The Journal of Neuroscience, March 1, 2003, 23(5):1825
Homeostatic Effects of Depolarization on Ca2+ Influx,
Synaptic Signaling, and Survival
Krista L.
Moulder,
Robert J.
Cormier,
Amanda A.
Shute,
Charles F.
Zorumski, and
Steven
Mennerick
Departments of Psychiatry and Neurobiology, Washington University
School of Medicine, St. Louis, Missouri 63110
Depolarization promotes neuronal survival through moderate
increases in Ca2+ influx, but the effects of
survival-promoting depolarization (vs conventional trophic support) on
neuronal signaling are poorly characterized. We found that chronic,
survival-promoting depolarization, but not conventional trophic
support, selectively decreased the somatic Ca2+
current density in hippocampal and cerebellar granule neurons. Depolarization rearing depressed multiple classes of high-voltage activated Ca2+ current. Consistent with the idea
that these changes also affected synaptic Ca2+
channels, chronic depolarization presynaptically depressed hippocampal neurotransmission. Six days of depolarization rearing completely abolished glutamate transmission but altered GABA transmission in a
manner consistent with the alterations of Ca2+
current. The continued survival of depolarization-reared neurons was
extremely sensitive to the re-establishment of basal culture conditions
and was correlated with the effects on intracellular Ca2+ concentration. Thus, compared with cells reared
on conventional trophic factors, depolarization evokes homeostatic
changes in Ca2+ influx and signaling that render
neurons vulnerable to cell death on activity reduction.
Key words:
depolarization; HVA Ca2+
current; glutamate; GABA; synaptic depression; neuronal survival
Copyright © 2003 Society for Neuroscience 0270-6474/03/2351825-07$05.00/0
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